Ledipasvir/Sofosbuvir looks good in HBV-coinfected patients

For patients with chronic hepatitis C and hepatitis B virus co-infection, 12 weeks of ledipasvir/sofosbuvir therapy achieved a 100 percent sustained viral response rate without causing liver failure or death in a phase 3b, multicenter, open-label study.

“Although we observed increases in HBV DNA in most patients, these increase were [usually] not associated with ALT [alanine amino transferase] flares or clinical complication.”

Although nearly two-thirds of patients developed HBV reactivation, less than 5 percent developed alanine aminotransferase rises at least twice the upper limit of normal, and only one patient had symptomatic HBV reactivation, which entecavir therapy solved. This study was the first to prospectively evaluate the risk of HBV reactivation during HCV treatment, the researchers wrote.

Because chronic hepatitis C virus infection tends to suppress HBV replication, peginterferon/ribavirin or direct-acting anti-HVC treatment can reactivate HBV infection, especially in patients who test positive for hepatitis B surface antigen (HBsAg). Left untreated, reactivated HBV can lead to fulminant hepatitis, liver failure, and death, as noted on recently mandated boxed warnings.

Accordingly, guidelines recommend testing patients for HBV infection before starting HCV treatment. The study enrolled 111 coinfected patients; about two-thirds were female, and 16 percent had compensated cirrhosis. All tested positive for HBsAg at screening, and all but one also tested positive at baseline. Mean baseline HBV DNA levels were 2.1 log10 IU/mL. Patients received 90 mg ledipasvir plus 400 mg sofosbuvir for 12 weeks, and levels of HCV RNA, HBV DNA, and HBsAg were tested at weeks 1,2,3,4,8,12, post treatment week 4, and then every 12 weeks until post treatment week 108.

In all, 70 (63 percent) patients developed HBV reactivation, including 84 percent of the 37 patients with undetectable HBV DNA at baseline. During treatment, none of these patients had ALT rise more than twice the upper limit of normal.

By 48 weeks post treatment, however, 77 percent still had quantifiable HBV DNA, and two had marked ALT rises. Furthermore, by post treatment week 53, one of these patients developed bilirubinemia and symptomatic HBV infection (malaise, anorexia, sclera jaundice, and nausea), which resolved after treatment with entecavir.

A total of 74 patients had quantifiable baseline HBV DNA (at least 20 IU/mL). Three received entecavir or tenofovir disoproxil fumarate based on confirmed HBV reactivation with a concomitant ALT rise of at least twice the upper limit of normal. All were asymptomatic. There were no cases of liver failure or death.

“Regardless of HBV DNA and/ or ALT elevations, no patient had signs of liver failure,” the researchers wrote. “Our results support the recommendations put forth in clinical treatment guidelines: HCV-infected patients should be evaluated for HBV infection prior to HCV treatment with direct-acting antivirals. Those who are HBsAg positive should be monitored during and after treatment for HBV reactivation, and treatment should be initiated in accordance with existing guidelines.”